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R. Bouhenni, D. P. Edward, S. Al Shahwan, J. Morales, B. Wakim; Identification of Unique Differentially Expressed Proteins in the Aqueous Humor of Patients With Primary Congenital Glaucoma (PCG). Invest. Ophthalmol. Vis. Sci. 2010;51(13):2672.
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© ARVO (1962-2015); The Authors (2016-present)
We previously hypothesized that altered aqueous humor (AH) components in PCG may cause some of the anatomic abnormalities seen in the disorder (Exp Eye Res. 2006, 82:24-32). To test this hypothesis we used label-free Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) to characterize the protein profiles of AH in PCG and normal patients.
Differential expression of proteins was examined by LC-MS/MS in AH from normal (n=4) and PCG (n=4) subjects. Data was analyzed using SEQUEST. Proteins with 2 or more peptide hits and an Xcorr of 2.5 and higher were selected for further analysis. Relative quantitation was determined based on peptide spectral counts for each protein. Pathway Studio 6.0 TM was used tomap the differentially expressed proteins into signaling pathways and functional categories. LC-MS/MS results were confirmed using western blot. Student t testwas used for the statistical analyses of data.
Proteins with altered expression in PCG included Glutathione Peroxidase 3 precursor (GPX3) which was absent in all PCG samples compared to control, Angiotensinogen precursor and Serum-derived hyaluronan-associated protein (ITIH2) were detected in all PCG and not in any of the control samples. Vitamin D-binding protein (VDBP), Serpin A1, Apolipoprotein A1, Apolipoprotein E, Serrotransferrin, Hemopexin and complement C3 were 2 fold higher (P<0.05) and Serpin C1 and Complement A-IV were 4 fold (P=0.01) and 3 fold (P=0.03) higher in PCG compared to control respectively. Prostaglandin-H2 D-isomerase precursor (PGDS2), The Interphotoreceptor Retinoid-binding protein (IRBP) and Opticin were 2 fold lower (P<0.05). Pathway studio analysis showed significant changes in some functional groups and metabolic pathways. The functional groups with significant representation in PCG were lipid transport, prostaglandin/thromboxane synthesis and extracellular matrix (ECM) remodeling. The metabolic pathway that appeared affected in PCG was the Angiogenesis R -> STAT signaling pathway.
Significant alterations in PCG AH proteome were found. The differentially expressed proteins are involved in inflammation/development, lipid transport and metabolism, ECM remodeling and oxidative stress; and some have been implicated in the pathogenesis of other forms of glaucoma. These proteins represent potential biomarkers and may play a role in the pathogenesis of PCG.
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